FIELD: chemistry.
SUBSTANCE: invention relates to a compound of formula I, including stereoisomers, geometric isomers, tautomers or pharmaceutically acceptable salts thereof: where Z1 is CR1; Z2 is CR2; Z3 is CR3 or N; Z4 is CR4 or N; where (i) X1 is N and X2 is S or (iv) X1 is S and X2 is CR7; R1, R2, R3, R4 and R7 are independently selected from H, F, Cl, Br, I, -CN, -CH2OR10, -(C1-C12 alkylene)NR10R11, -(C1-C12 alkylene)NR12C(=O)R10, -CO2R10, -C(=O)N(R10)OR11, -NR10R11, -C(=O)NR10R11, -C(=O)NR10(C1-C12 alkylene)NR10R11, -C(=O)NR10(C1-C12 alkylene)NR10C(=O)OR11, -C(=O)NR10(C1-C12 alkylene)NR10C(=O)R11, -C(=O)NR10(C1-C12 alkylene)R11, -C(=O)NR10(C1-C12 alkylene)R10, -C(=NR10)NR10R11, -NR12C(=O)R10, -NR12C(=O)OR11, -NR12C(-O)NR10R11, -NR12C(=O)(C1-C12 alkylene)NR10R11, NR12(C=O)C1-C12 alkylene)NR11(C=O)R12, -C≡CR10, C1-C20 heteroaryl, said heteroaryl being an unsaturated carbocyclic residue containing 5-6 ring atoms, where 1-4 ring atoms are nitrogen atoms, and phenyl, where the heteroaryl and phenyl are optionally substituted with one or two groups selected from -CH2OH, -(CH2)2OH, -CH2CO2H, -CN, -CH2NH2, -(CH2)2N(CH3)2, -CH3, -CO2H, -CH2CO2CH3, -NH2 and -S(O)2CH3; A is selected from -C(=O)NR5R6, -C(=S)NR5R6, phenyl and C1-C20 heteroaryl, said heteroaryl being an unsaturated carbocyclic residue containing 5-10 ring atoms, 1-4 of which are heteroatoms selected from nitrogen, oxygen or sulphur, C1-C20 heteroaryl and phenyl are optionally substituted with one or three groups independently selected from C1-C12 alkyl, -(C1-C12 alkylene)NR10R11, -CH3, oxo, -CO2CH3, -NH2, 1-methylpiperid-4-yl, isopropyl, isobutyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, benzoimidazolyl, benzyl and phenyl, where the alkyl, benzoimidazolyl and phenyl are optionally substituted with one or more groups independently selected from F, Cl, Br, I, -CF3, -CH2OH, -CH3, -C(=O)NHCH3, -NH2, -OH, -OCH3, -CH2OCH3, -C(=O)N(CH3)2, -N(CH3)2, -C(CH3)2OH, -CH(CH3)2, -CH2(1H-1,2,4-triazol-5-yl) and C(=O)4-methylpiperazin-1-yl; R5 is selected from C1-C12 alkyl, optionally substituted with one group independently selected -NH2, -NHCOCH3 and -OH; R6 is selected from pyridinyl and phenyl, each optionally substituted with one or two groups independently selected from F, Cl, Br, I, -CN, -CF3, -C(=O)NR10R11, -C(=O)NR10(C1-C12 alkylene)NR10R11 and -C(=O)NR10R11; R10, R11 and R12 are independently selected from H, C1-C12 alkyl, C1-C12 alkylene-phenyl, cyclopentyl, pyridinyl and imidazolyl, where C1-C12 alkyl, cyclopentyl are optionally substituted with one or two groups independently selected from -CH2OH, -N(CH3)2, -NHCOCH3, -OH and -S(O)2CH3; or R10 and R11 together with a nitrogen atom to which they are bonded form a C5-C6 heterocyclic ring containing one or two heteroatoms selected from nitrogen and oxygen, or pyrazolyl, optionally substituted with one or two groups independently selected -CH3, -NH2, -N(CH3)2; -OH and oxo. The invention also relates to a pharmaceutical composition having PI3K inhibiting activity based on said compounds.
EFFECT: obtaining novel compounds which can be used in medicine for treating cancer.
25 cl, 5 dwg, 2 tbl, 331 ex
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Authors
Dates
2014-02-10—Published
2009-03-30—Filed